Antiphospholipid Antibodies, Platelet and Endothelial Activation in Acute Thrombotic Thrombocytopenic Purpura (TTP).

BACKGROUND. Although the etiology of TTP remains controversial, some notable associated conditions have been identified. These include genetic predisposition, infections, drugs, pregnancy, systemic lupus erythematosus (SLE) and deficiency of ADAMTS13. These associations underscore the suspected immunological nature of this disorder. Some authors have reported the presence of antiphospholipid antibodies (APLA) with onset of fulminate severe TTP. Also, platelet and endothelial activation has been described in TTP but their possible relation with APLA is unknown.

METHODS. We measured APLA in 19 patients with acute TTP and 17 in remission. Fifteen were female and four were male, mean age of 37 ± 15. All met the diagnostic criteria of TTP and were treated with standard therapy including exchange plasmapheresis. The severity of TTP was classified based on duration of hospitalization and numbers of plasmapheresis needed. Recurrence of TTP was assessed by history and review of medical records. CBC, platelet counts, blood chemistry and LDH were monitored. We investigated APLA antibodies IgG and IgM against 6 antigens (β2GP1, FVII/VIIa, CL, PC, PS, PE) by ELISA. To investigate platelet activation, we measured by flow cytometry: CD62P on platelets, and platelet microparticles (PMP) by CD41 (PMP41). We also measured endothelial microparticles (EMP) using CD62E.

RESULTS.

Lab study: In acute TTP, 42% (8/19) were APLA positive for at least one IgG antibody. The most frequent was aPS (33%) followed by aCL(28%), aPC(28%), aβ2GP1 (28%), FVII/VIIa (21%) and PE (21%). IgM antibodies were not detected. APLA was two-fold more prevalent in acute TTP (42%) than in remission (21%). In acute TTP multiple antibodies (two or more) were seen in 75% (6/8) while in remission only one (12.5%) had multiple antibodies. Platelet activation measured by CD62P was higher in APLA+ than in APLA− (102 ± 25 vs 33 ± 8 fluorescence units, p<0.02, X ± SEM). PMP41 was higher in APLA+ than in APLA− but this difference was not significant. We also found that EMP62E was significantly higher in APLA+ than in APLA− patients (p<0.01).

Clinical observations: When comparing the two groups (APLA+ vs APLA−), APLA+ group had higher incidence of recurrence of TTP than APLA− (75% vs 36%), p<0.05. Platelet counts, LDH, severity and incidence of CNS syndrome were not significantly different between APLA+ and APLA− groups.

CONCLUSIONS: APLA are frequently seen in acute TTP (42%) and they tend to decline in remission. Their presence is associated with increased activation of platelets and endothelial cells, and also with clinical recurrence of TTP. APLA may play a role in excerbation and recurrence of TTP.